Effect of Serum Deprivation Stress on Signal Induction Regulatory Protein-Alpha (SIRP-Alpha)-Mediated Erythrophagocytosis by Macrophages.

IF 1.5 Q3 MEDICINE, RESEARCH & EXPERIMENTAL
Zakaria Hindi, AbdAllah Gad, Courtney Jarvis, Talal Zahoor, Craig Spellman, Stephanie Filleur
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Abstract

BACKGROUND Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome that involves loss of macrophages' self-cells recognition resulting in auto-phagocytosis of erythrocytes, leukocytes, and platelets and leading to multi-system effects. The pathogenesis of HLH is unclear but can be explained by malfunction of the physiologic inhibitory pathway through interaction between macrophage SIRP-alpha and erythrocyte CD 47. The goal of the present study was to evaluate if erythrocytes phagocytosis occurs as a result of altered macrophage SIRP-alpha expression during inflammatory/stressful conditions as seen in HLH. MATERIAL AND METHODS RAW264.7 macrophages were cultured in serum-free media (SFM) and complete media (CM) to simulate stressful and physiologic conditions, respectively. CD47+ mouse erythrocytes were used to test interactions with macrophages at different stages. SIRP-alpha expressions and phagocytosis assays were measured and analyzed at different steps. The study was in vitro and used murine cells to simulate in vivo human interactions. RESULTS SIRP-alpha expressions and phagocytosis rates were higher in SFM compared to CM. Interestingly, after adding SIRP-alpha blocking antibodies (Ab), phagocytosis rates significantly decreased. CONCLUSIONS Serum deprivation and LPS/INF-Gamma induction resulted in increased SIRP-alpha expression and erythrophagocytosis. Using SIRP-alpha Ab during this condition decreased the rate of erythrophagocytosis, which indicates that SIRP-alpha receptor can have pro-phagocytic activity.

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血清剥夺应激对信号诱导调节蛋白α(SIRPα)介导的巨噬细胞红吞噬作用的影响。
背景血吞噬性淋巴组织细胞增多症(HLH)是一种罕见的综合征,涉及巨噬细胞自身细胞识别的丧失,导致红细胞、白细胞和血小板的自身吞噬,并导致多系统效应。HLH的发病机制尚不清楚,但可以通过巨噬细胞SIRPα和红细胞CD47之间的相互作用来解释生理抑制途径的功能障碍。本研究的目的是评估红细胞吞噬作用是否是由于炎症/应激条件下巨噬细胞SIRPα表达的改变而发生的,如在HLH中所见。材料和方法RAW264.7巨噬细胞分别在无血清培养基(SFM)和完全培养基(CM)中培养,以模拟应激和生理条件。CD47+小鼠红细胞用于测试不同阶段与巨噬细胞的相互作用。在不同步骤测量和分析SIRPα的表达和吞噬作用测定。这项研究是在体外进行的,并使用小鼠细胞模拟体内人类相互作用。结果与CM相比,SFM中SIRPα的表达和吞噬率较高。有趣的是,添加SIRPα阻断抗体(Ab)后,吞噬率显著降低。结论血清剥夺和LPS/INFγ诱导导致SIRPα表达增加和红细胞吞噬作用增强。在这种情况下使用SIRPαAb降低了红细胞吞噬作用的速率,这表明SIRPα受体可以具有促吞噬活性。
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来源期刊
Medical Science Monitor Basic Research
Medical Science Monitor Basic Research MEDICINE, RESEARCH & EXPERIMENTAL-
CiteScore
6.00
自引率
0.00%
发文量
16
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